Abstract

BackgroundSchizophrenia is a severely multifactorial neuropsychiatric disorder, and the majority of cases are due to genetic variations. In this study, we evaluated the genetic association between the C-Maf-inducing protein (CMIP) gene and schizophrenia in the Han Chinese population.MethodsIn this case-control study, 761 schizophrenia patients and 775 healthy controls were recruited. Tag single-nucleotide polymorphisms (SNPs; rs12925980, rs2287112, rs3751859 and rs77700579) from the CMIP gene were genotyped via matrix-assisted laser desorption/ionization time of flight mass spectrometry. We used logistic regression to estimate the associations between the genotypes/alleles of each SNP and schizophrenia in males and females, respectively. The in-depth link between CMIP and schizophrenia was explored through linkage disequilibrium (LD) and further haplotype analyses. False discovery rate correction was utilized to control for Type I errors caused by multiple comparisons.ResultsThere was a significant difference in rs287112 allele frequencies between female schizophrenia patients and healthy controls after adjusting for multiple comparisons (χ2 = 12.296, Padj = 0.008). Females carrying minor allele G had 4.445 times higher risk of schizophrenia compared with people who carried the T allele (OR = 4.445, 95% CI [1.788–11.046]). Linkage-disequilibrium was not observed in the subjects, and people with haplotype TTGT of rs12925980–rs2287112–rs3751859–rs77700579 had a lower risk of schizophrenia (OR = 0.42, 95% CI [0.19–0.94]) when compared with CTGA haplotypes. However, the association did not survive false discovery rate correction.ConclusionThis study identified a potential CMIP variant that may confer schizophrenia risk in the female Han Chinese population.

Highlights

  • Schizophrenia (SCZ) is a severely multifactorial neuropsychiatric disorder that affects almost 1% of adults around the world

  • We conducted a genetic association study stratified by gender to examine the association between tag single-nucleotide polymorphisms (SNPs) of the C-Maf-inducing protein (CMIP) gene and SCZ in the Han Chinese population

  • The genotypic distribution of rs2287112 was found to be significantly different between SCZ patients and healthy controls (P = 0.016), but the difference did not survive the false discovery rate (FDR) correction adjusted for the multiple comparison (Padj = 0.128)

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Summary

INTRODUCTION

Schizophrenia (SCZ) is a severely multifactorial neuropsychiatric disorder that affects almost 1% of adults around the world. SCZ has devastating impacts on patients’ and their families’ quality of life. Genetic factors play a major role in SCZ etiology (Owen, Sawa & Mortensen, 2016) and genetic variations in chromosome 16 are associated with a variety of neuropsychiatric disorders. Previous studies found that regions on chromosome 16q may increase susceptibility to SCZ (Lewis et al, 2003), bipolar disorder (Lewis et al, 2003), and autism (Wassink et al, 2008). Gender-specific associations between gene SNPs (i.e., RELN, GABRB3 and MTHFR) and SCZ have been found in several other studies (Sozuguzel & Sazci, 2019; Wan et al, 2019; Liu et al, 2018). We conducted a genetic association study stratified by gender to examine the association between tag SNPs of the CMIP gene and SCZ in the Han Chinese population

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